title: Tissue inhibitor of metalloproteinase-1 modulates allergic lung inflammation in murine asthma.
abstract: Matrix metalloproteinases (MMPs) modulate development, inflammation, and repair in lungs. Tissue inhibitors of MMPs (TIMPs) interact with MMPs, controlling the intensity and nature of the response to injury. Absence of MMP-9, -2, and -8 activities is associated with altered lung inflammation during allergic sensitization. To test the hypothesis that the absence of TIMP-1 enhances allergic lung inflammation, airway hyperreactivity (AHR), and lung remodeling in asthma, we studied TIMP-1 null (TIMP-1 KO) mice and their WT controls using an ovalbumin (OVA) asthma model. TIMP-1 KO mice, compared to WT controls, developed an asthma phenotype characterized by AHR, pronounced cellular lung infiltrates, greater reduction in lung compliance, enhanced Th2 cytokine mRNA and protein expression, and altered collagen lung content associated with enhanced MMP-9 activity. Our findings support the hypothesis that TIMP-1 plays a protective role by preventing AHR and modulating inflammation, remodeling, and cytokine expression in an animal model of asthma.
authors.affiliation: VA Western New York Healthcare System, Buffalo, NY 14215, USA. mfsands@buffalo.edu
authors.forename: Mark F
authors.initials: MF
authors.lastname: Sands
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Ohtake
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
authors.forename: Shervin S
authors.initials: SS
authors.lastname: Takyar
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Aalinkeel
authors.forename: Yisheng V
authors.initials: YV
authors.lastname: Fang
authors.forename: Jessica W
authors.initials: JW
authors.lastname: Blume
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Mullan
authors.forename: Don E
authors.initials: DE
authors.lastname: Sykes
authors.forename: Sandra
authors.initials: S
authors.lastname: Lachina
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004195:Disease Models, Animal; D015870:Gene Expression; D006909:Hydroxyproline / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D007073:Immunoglobulin E; D010047:Ovalbumin; D006909:Hydroxyproline